1. Field of the Invention
This invention relates to new anthracycline glycoside antitumor antibiotics, to methods for their preparation and recovery, to pharmaceutical compositions containing them and to methods of using said antibiotics as antibacterial and antitumor agents.
2. Description of the Prior Art
A number of anthracycline glycosides have been described in the literature. Among them, daunomycin and adriamycin have already been applied clinically for treatment of human cancers. Preparation of adriamycin by fermentation of S. peuceticus var. caesius is disclosed in U.S. Pat. No. 3,590,029. Chemical conversion of daunomycin to adriamycin is taught in U.S. Pat. No. 3,803,124. Daunomycin (produced by fermentation of S. peuceticus in U.K. Pat. No. 1,003,383) may be the same as Rhone-Poulenc's 13,057 R.P. (formerly rubidomycin and now daunorubicin; see U.K. Pat. No. 985,598, 1,188,262 and 1,241,750 and U.S. Pat. No. 3,616,242) and is probably identical to Ciba's danubomycin disclosed in U.S. Pat. No. 3,092,550 and U.K. Pat. No. 901,830. See also U.S. Pat. No. 3,092,550 and U.K. Pat. No. 901,830. See also U.S. Pat. No. 3,686,163 on dihydrodaunomycin.
Cinerubin A and cinerubin B, glycosides of the aglycone, .epsilon.-pyrromycinone, are disclosed in U.K. Pat. No. 846,130 [see also U.S. Pat. No. 3,864,480 and Keller-Schierlein et al., Antimicrobial Agents and Chemotherapy, page 68 (1970) and Chemical Abstracts, 54, 1466i (1960)].
Aclacinomycin A and B having the aglycone, aklavinone, are disclosed in U.S. Pat. No. 3,988,315.
The anthracycline glycoside, carminomycin, described in J. Antibiotics, 27, 254-259 (1974), in J. Amer. Chem. Soc., 97 (20), 5955-5956 (1975) and in U.K. Pat. No. 1,426,637 has been reported to be active against several animal tumor systems.
Pyrromycin, an anthracycline glycoside containing the aglycone, .epsilon.-pyrromycinone, and the glycosidic sugar, rhodosamine, is disclosed in Chem. Ber., 92, 1904-1909 (1959).
Galirubin A having the aglycone, .epsilon.-pyrromycinone, is disclosed in Chemical Abstracts, 64, 3896 g (1966) and Chemical Abstracts, 67, 90573z (1967).
Rutilantin having the aglycone, .epsilon.-pyrromycinone, is disclosed in Biochem. J., 81, 101-104 (1961).
For further illustrative and summary disclosures of anthracycline antibiotics see Index of Antibiotics from Actinomycetes, Hamao Umezawa, Editor-in-Chief, University Park Press, State College, Pennsylvania, U.S.A. (1967) as follows:
______________________________________ Antibiotic Page No. ______________________________________ Aklavin 111 Cinerubin A 220 Cinerubin B 221 Danubomycin 242 Daunomycin 243 Pyrromycin 542 Rhodomycin A, B 561 Rubidomycin 574 ______________________________________
The textbook Antibiotics, Volume 1, Mechanism of Action, edited by David Gottlieb and Paul D. Shaw, Springer-Verlag New York, Inc., New York, New York (1967) at pages 190-210 contains a review by A. DiMarco entitled "Daunomycin and Related Antibiotics".
Information Bulletin, No. 10, International Center of Information of Antibiotics, in collaboration with WHO, December, 1972, Belgium, reviews anthracyclines and their derivatives.